This invention pertains to the preparation of 3-furoate esters and to certain novel intermediate compounds. More particularly, this invention pertains to a two-step process wherein a 4-acyl-2,3-dihydrofuran is converted to a 2-alkoxy-3-acyl-3-halotetrahydrofuran which then is contacted with an alkoxide to produce an alkyl 3-furoate. The 2-alkoxy-3-acyl-3-halotetrahydrofuran intermediates are novel compounds.
Unlike 2-furoic acid and its esters which are derived from inexpensive furfural, 3-furoic acid and its esters have been, in the past, difficult and expensive to synthesize in any amount. Preparation of 3-substituted furans from furan itself requires multiple steps because the 2-position of furan is more activated toward aromatic substitution reactions. Although several literature references describe methods to produce 3-substituted furans, many contain comments on the difficulty of synthesizing such compounds. For example, S. P. Tanis states in Tetrahedron Letters, 23, 3115-3118 (1982): "Although many methods have been reported for the synthesis of 3-substituted furans they generally require many steps, relatively inaccessible starting materials, or proceed in low overall yields."
Most literature processes for the preparation of 3-furoic acid or ester involve the decarboxylation of furandicarboxylic acids. T. Reichstein, et al., Helv. Chim. Acta, 15, 268-273 (1932); 16, 276-281 (1933), reported the preparation of 3-furoic acid from either furan-2,3-dicarboxylic acid, furan-3,4-dicarboxylic acid or furan-2,4-dicarboxylic acid. These dicarboxylic acids are obtained in low yield via several intermediate steps. See also D. Dare, et al., J. Chem. Soc., Perkin I, 1130-1134 (1973); M. Boyd, et al., Synthesis, 545-546 (1971); L. W. Deady, et al., Synthesis, 571 (1972). In a simplification of Reichstein's process, E. Sherman, et al. decarboxylated furantetracarboxylic acid to give 3-furoic acid (J. Am. Chem. Soc., 72, 2195-2199 (1950)). Gilman, et al., J. Am. Chem. Soc., 55, 2903-2909 (1933) reported the decarboxylation of 2,4-furandicarboxylic acid to 3-furoic acid which was converted to ethyl 3-furoate via 3-furoyl chloride.
3-Bromofuran can be converted into 3-furoic acid by reaction with butyl lithium to give 3-lithiofuran followed by reaction with carbon dioxide (Y. Fukuyama, et al., Synthesis, 443-444 (1974); I. Fleming, et al., Synthesis, 898 (1985)) or by electrocarboxylation (O. Sock, et al., Tetrahedron Letters, 26, 1509-1512 (1985)). These methods, however, are expensive and difficult to adapt to commercial scale operation. Additionally, 3-bromofuran is prohibitively expensive for use as a starting material.
Other processes for preparing 3-furoic acid and esters thereof include (1) the rhodium-catalyzed reaction of alkyl formyldiazoacetate with vinyl ethers (E. Wenkert, et al., J. Organic Chem., 55, 4975-4976 (1990)); (2) Diels Alder reactions of oxazoles with propiolic acid or ester (S. R. Ohlsen, et al., J. Chem. Soc. (C), 1632-1633 (1971); G. Ya. Kondrat'eva, et al., Proc. of the Academy of Sciences, USSR (Chem.), 200, 862-864 (1971)); and (3) oxidative addition of ethyl formylacetate with vinyl acetate (E. Baciocchi, et al., Synthetic Communications, 18, 1841-1846 (1988)). These processes suffer from the use of expensive and/or hazardous starting materials and low yields.
F. Effenberger, et al., Chem. Ber., 115, 2766-2782 (1982) and M. Hojo, et al., Synthesis, 1016-1017 (1986) describe the trichloroacetylation and trifluoroacetylation of 2,3-dihydrofuran to produce 2,3-dihydro-4-trichloroacetylfuran and 2,3-dihydro-4-trifluoroacetylfuran in good yield. These trihalomethylketone intermediates can be hydrolyzed to yield 2,3-dihydro-4-furoic acid (M. Hojo, et al., Synthesis, 1016-1017 (1986); N. Zanatta, et al., J. Heterocyclic Chem., 34, 509-513 (1997)). P. Maynard-Faure, et al., Tetrahedron Letters, 39, 2315-2318 (1998) have shown that the trichloromethylketone intermediates can be converted into their esters, i.e., alkyl 2,3-dihydro-4-furoates, by treatment with an alcohol and potassium carbonate.
Methyl 3-furoate has been produced in 18% yield by the bromination of methyl 2,3-dihydro-4-furoate with N-bromosuccinimide followed by heating with 50% aqueous potassium hydroxide (J. T. Wrobel, et al., Rocz. Chem., 40, 1005-1018 (1966)). Methyl and ethyl 2,3-dihydro-4-furoate have been brominated with bromine to give methyl and ethyl 2,3-dibromo-tetrahydro-3-furoate (W. Hasenbrink, Liebigs Ann. Chem., 468-476 (1974)). These dibromides can be dehydrobrominated to produce methyl and ethyl 3-furoate but the yield is low and side-products require separation.